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Urothelial CarcinomaPhase 1/2NCT02769962

Trial of EP0057, a Nanoparticle Camptothecin With Olaparib in People With Relapsed/Refractory Small Cell Lung Cancer

A Phase 1/2 study testing EP0057, olaparib and CT scan in people with Urothelial Carcinoma and Urothelial Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Background: EP0057 (formerly CRLX101) consists of a sugar molecule cyclodextrin linked to a chemotherapy drug called camptothecin. The combined molecule or "nanoparticle drug conjugate" travels through the blood. Once inside cancer cells, the chemotherapy drug is released from the molecule. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
EP0057, olaparib and CT scan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteUnited States
Study dates
9 May 2016to 4 Mar 2025
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically or cytologically confirmed advanced solid tumor that is resistant or refractory to standard therapy.
  • A minimum of 2 weeks will be required from any prior therapy, including chemotherapy, immunotherapy and/or radiation. In addition, recovery to Grade <= 1 from all reversible toxicities related to prior therapy is required at study entry.
  • Patients do not need to have measurable disease to enroll on phase I.
  • Age 18 years.
  • Eastern cooperative Oncology Group (ECOG) performance status <=2
  • Patients with treated brain metastases (surgery, whole or stereotactic brain radiation) are allowed provided the lesions have been stable for at least 2 weeks and the patient is off steroids or is on a stable dose of steroids. Patients with brain metastases should not require use of enzyme-inducing antiepileptic drugs (e.g., carbamazepine, phenytoin, or phenobarbital) within 14 days before first dose and during study. Use of newer antiepileptics that do not produce enzyme induction drug-drug interactions (DDIs) is allowed.
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  • Patients must have normal organ and marrow function as defined below:
  • leukocytes >=3,000/mcL
  • absolute neutrophil count >=1,500/mcL without growth factor support
  • platelets >=100,000/mcL without growth factor support
  • hemoglobin >=9 g/dL, and no blood transfusion within 4 weeks.
  • OR
  • Hemoglobin >10 g/dL, and no blood transfusion within 2 weeks.
  • total bilirubin <=1.5 x upper limit of normal (ULN) (unless Gilbert's Disease)
  • Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT)<=2.5 X institutional upper limit of normal (<= 5X ULN if liver mets)
  • creatinine <= ULN
  • OR
  • creatinine clearance >= 51 mL/min (calculated using the Cockroft-Gault formula) for patients with creatinine levels above institutional normal.
  • -The effects of EP0057 (formerly CRLX101) and olaparib on the developing human fetus are unknown. For this reason and because these agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 120 days (both male and female) following last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Fertile females of childbearing potential are defined as women physically capable of becoming pregnant unless the female patient cannot have children because of surgery or other medical reasons (effective tubal ligation, ovaries or the uterus removed, or are post-menopausal). Post-menopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments,
  • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for women under 50,
  • radiation-induced oophorectomy with last menses >1 year ago,
  • chemotherapy-induced menopause with >1 year interval since last menses,
  • or surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Negative urine pregnancy test < =3 days prior to cycle 1 day 1 (C1D1) (women of childbearing potential only)
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • INCLUSION CRITERIA: - Phase II Small Cell Lung Cancer (SCLC)
  • Age >=18 years.
  • Patients must have histologically or cytologically confirmed diagnosis of SCLC from a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
  • Have received and progressed during or after a platinum-based standard chemotherapy regimen and/or an immune-checkpoint inhibitor
  • Patients could have received any number of therapies for relapsed or progressive disease, including re-treatment with original frontline regimen. A minimum of 2 weeks will be required from any prior therapy, including chemotherapy, immunotherapy and/or radiation. In addition, recovery to Grade <= 1 from all reversible toxicities related to prior therapy is required at study entry. No previous irradiation to the site of measurable or evaluable disease, unless that site had subsequent evidence of progression.
  • Patients must have measurable disease as per Response Evaluation Criteria in Solid Tumors, version (RECIST 1.1).
  • Radiographic evidence of disease progression after initial therapy should have been documented.
  • Eastern Cooperative Oncology Group (ECOG) performance status <=2.
  • Patients with treated brain metastases (surgery, whole or stereotactic brain radiation) are allowed provided the lesions have been stable for at least 2 weeks and the patient is off steroids or is on a stable dose of steroids. Patients with brain metastases should not require use of enzyme-inducing antiepileptic drugs (e.g., carbamazepine, phenytoin, or phenobarbital) within 14 days before first dose and during study. Use of newer antiepileptics that do not produce enzyme induction drug-drug interactions (DDIs) is allowed.
  • Patients must have normal organ and marrow function as defined below:
  • Leukocytes >=3,000/mcL
  • absolute neutrophil count >=1,500/mcL without growth factor support
  • platelets >=100,000/mcL without growth factor support
  • hemoglobin >=9 g/dL, and no blood transfusion within 4 weeks.
  • OR
  • hemoglobin >10 g/dL, and no blood transfusion within 2 weeks.
  • total bilirubin <=1.5 x upper limit of normal (ULN) (unless Gilbert's Disease)
  • AST(SGOT)/ALT(SGPT) <=2.5 X institutional upper limit of normal (<= 5X ULN if liver mets)
  • creatinine <= ULN
  • OR
  • creatinine clearance >=51 mL/min (calculated using the Cockroft-Gault formula) for patients with creatinine levels above institutional normal.
  • The effects of EP0057 and olaparib on the developing human fetus are unknown. For this reason and because these agents are known to be teratogenic, women of child-bearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 120 days (both male and female) following last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Fertile females of childbearing potential are defined as women physically capable of becoming pregnant unless the female patient cannot have children because of surgery or other medical reasons (effective tubal ligation, ovaries or the uterus removed, or are post-menopausal). Post-menopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments,
  • LH and FSH levels in the post-menopausal range for women under 50,
  • radiation-induced oophorectomy with last menses >1 year ago,
  • chemotherapy-induced menopause with >1 year interval since last menses,
  • or surgical sterilization (bilateral oophorectomy or hysterectomy).
  • INCLUSION CRITERIA: for Urothelial Carcinoma Expansion Cohort (accrual to the cohort ended with amendment version 08/17/2022)
  • Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis from a CLIA-certified laboratory, with measurable disease by RECIST (version 1.1) including lymphadenopathy and visceral metastatic disease
  • Male or female patients >= 18 years of age.
  • Patient must have received at least one platinum-based regimen of chemotherapy and/or an immune-checkpoint inhibitor if appropriate with progressive disease.
  • Prior antiangiogenic and radiation therapy are permitted (2-week washout from therapy is required).
  • Bisphosphonates and denosumab are permitted if on a stable dose for >=4 weeks.
  • ECOG 0-2
  • Patients must have normal organ and marrow function as defined below:
  • leukocytes >=3,000/mcL
  • absolute neutrophil count >=1,500/mcL without growth factor support
  • platelets >=100,000/mcL without growth
  • factor support
  • hemoglobin >=9 g/dL, and no blood transfusion within 4 weeks.
  • OR
  • hemoglobin >10 g/dL, and no blood transfusion within 2 weeks.
  • total bilirubin<TAB> <=1.5 x ULN (unless Gilbert's Disease)
  • AST(SGOT)/ALT(SGPT) <=2.5 X institutional upper limit of normal (<= 5X ULN if liver mets)
  • creatinine <= ULN
  • -The effects of EP0057 and olaparib on the developing human fetus are unknown. For this reason and because these agents are known to be teratogenic, women of child-bearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 120 days (both male and female) following last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Fertile females of childbearing potential are defined as women physically capable of becoming pregnant unless the female patient cannot have children because of surgery or other medical reasons (effective tubal ligation, ovaries or the uterus removed, or are post-menopausal). Post-menopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments,
  • LH and FSH levels in the post-menopausal range for women under 50,
  • radiation-induced oophorectomy with last menses >1 year ago,
  • chemotherapy-induced menopause with >1 year interval since last menses,
  • or surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of olaparib.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Willingness to release archival tissue sample for research purposes, if available
  • INCLUSION CRITERIA for mCRPC Expansion Cohort (accrual to the mCRPC cohort ended with amendment version 7/27/2021)
  • Patients must have metastatic, progressive, castrate resistant prostate cancer (mCRPC).
  • Documented histopathological confirmation of prostate cancer from a CLIA-certified laboratory.
  • All patients must have at least one lesion deemed safe to biopsy and be willing to undergo a mandatory baseline biopsy.
  • Patients must have received prior treatment with enzalutamide and/or abiraterone with the exception of patients who were treated with docetaxel and androgen deprivation therapy for metastatic castrate-sensitive prostate cancer and progressed on docetaxel treatment or who progress within one month of the last docetaxel dose.
  • Patients must have castrate levels of testosterone (<50 ng/dl [1.74 nmol/l])
  • Patients must have undergone bilateral surgical castration or must agree to continue on gonadotropin-releasing hormone (GnRH) agonists/antagonists for the duration of the study.
  • ECOG performance status <= 2
  • Patients must have adequate bone marrow, hepatic, and renal function with:
  • leukocytes >=3,000/mcL
  • absolute neutrophil count >=1,500/mcL without growth factor support
  • platelets >=100,000/mcL without growth factor support
  • Hemoglobin >=9 g/dL, and no blood transfusion within 4 weeks.
  • OR
  • hemoglobin >10 g/dL, and no blood transfusion within 2 weeks.
  • total bilirubin <=1.5 x ULN (<=3 (SqrRoot) ULN for subjects with Gilbert's Disease)
  • AST(SGOT)/ALT(SGPT) <=3 X institutional upper limit of normal (<= 5X ULN if liver mets)
  • creatinine <= ULN
  • OR
  • --creatinine clearance >=51 mL/min (calculated using the Cockroft-Gault formula) for patients with creatinine levels above institutional normal.
  • Men must be at least 18 years of age.
  • Patient must be capable of understanding and complying with protocol requirements and is willing to give informed consent.
  • Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation and for 120 days after last dose of study drug. Sexually active subjects and their female partners must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 3 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must also agree to use both a barrier method and a second method of birth control during the course of the study and for 3 months after the last dose of study drug(s). Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.
  • Patients who were treated for metastatic castrate-sensitive prostate cancer with docetaxel and androgen deprivation therapy who progress on docetaxel treatment or who progress within one month of the last docetaxel dose are eligible.
  • EXCLUSION CRITERIA: - Phase I and II SCLC and UC Expansion Cohort (note: accrual to the UC cohort ended with amendment version 08/17/2022)
  • Patients who are receiving any other investigational agents.
  • Persistent toxicities (>= Common Terminology Criteria for Adverse Events (CTCAE) grade 2) with the exception of alopecia and neuropathy, caused by previous cancer therapy
  • Patients who have had prior treatment with olaparib or other camptothecin inhibitors (Ulcerative Colitis (UC) expansion Cohort Only).
  • Patients with myelodysplastic syndrome/acute myeloid leukemia or active pneumonitis; or baseline features suggestive of myelodysplastic syndrome or acute myelogenous leukemia on peripheral blood smear or bone marrow biopsy, if clinically indicated.
  • Hypersensitivity to study therapies ...

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Phase I/II Trial of EP0057, a Nanoparticle Camptothecin With Olaparib in Patients With Relapsed/Refractory Small Cell Lung, Bladder and Prostate Cancers

Background: EP0057 (formerly CRLX101) consists of a sugar molecule cyclodextrin linked to a chemotherapy drug called camptothecin. The combined molecule or "nanoparticle drug conjugate" travels through the blood. Once inside cancer cells, the chemotherapy drug is released from the molecule. Olaparib is a drug that may stop cancer cells from repairing the deoxyribonucleic acid (DNA) damage caused by chemotherapy. Researchers want to see how safe it is to give EP0057 and olaparib together and to see how well the combination treats a specific type of lung cancer called small cell lung cancer (SCLC).

Objectives:

Read more

To test the safety and maximum dose of EP0057 and olaparib together. To test how well they treat small cell lung cancer.

Eligibility:

Adults 18 and older with small cell lung cancer.

Design:

Participants will be screened with standard cancer care tests.

Participants will get the 2 study drugs in 28-day cycles. EP0057 will be given every 2 weeks, through a small plastic tube in an arm vein. Olaparib will be taken by mouth twice a day most days. Participants will keep a pill diary.

For Cycle 1, participants will have 3 visits. All other cycles will have 2 visits.

At study visits, participants may have:

  • Blood and hair samples taken
  • History and Physical exam
  • Questions about health and side effects
  • Pregnancy test
  • Optional tumor biopsy where a piece of tumor is removed by needle after numbing the skin.
  • Computed tomography (CT) scan
  • Injection of EP0057 (twice per cycle)
  • Olaparib prescription

Participants will have a follow-up visit 4 weeks after finish taking the drugs. They will have a physical exam and blood tests. They may have a tumor biopsy. The study team will call the patient every 3 months for follow up after completing the study treatment.

Read the detailed description

Background:

  • Small cell lung cancer (SCLC) is an aggressive cancer with a poor prognosis.
  • Although highly responsive to chemotherapy initially, SCLC relapses quickly and becomes refractory to treatment within a few months.
  • Urothelial Carcinoma (UC) of the Bladder is the fourth most common malignancy in men and the ninth most common in women.
  • Prostate cancer is the most common cancer among men in the United States. While prostate cancer is initially responsive to androgen deprivation therapy (ADT), the median duration of sensitivity is 24-36 months. Moreover, patients develop resistance to current treatment options.
  • The use of poly adenosine diphosphate ribose polymerase (PARP) inhibitors in combination with chemotherapy builds upon pre-clinical data in lung cancer and other cancers supporting the notion that PARP inhibitors potentiate the effect of deoxyribonucleic acid (DNA) damaging therapies.
  • Despite their highly synergistic activity in preclinical models, human studies combining PARP inhibitors and camptothecins have not translated into clinical benefit due to enhanced toxicity with the combination.
  • One approach to improve ability to combine camptothecins with agents that sensitize their activity like PARP inhibitors is to use alternative formulations that minimize toxicity to the normal tissues.
  • EP0057 (formerly CRLX101) is a nanoparticle drug conjugate composed of 20 (S)-camptothecin (a potent and highly selective topoisomerase I inhibitor) conjugated to a linear, cyclodextrin polyethylene glycol-based polymer.
  • Olaparib is a PARP inhibitor indicated as monotherapy in patients with deleterious or suspected deleterious germline breast cancer gene (BRCA) mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Olaparib has an established safety profile, and it is under investigation in a number of different cancers.

Objectives:

  • Phase I: To determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of EP0057 in combination with olaparib in patients with refractory cancers.
  • Phase II: To determine the antitumor activity of olaparib plus EP0057 with respect to progression free survival at 16 weeks in SCLC patients with resistant or sensitive relapse.
  • Expansion Cohorts: To determine overall response rate of EP0057 plus olaparib in patients with mCRPC and urothelial carcinoma.

Eligibility:

Phase I

  • Adult patients >=18 years of age
  • Histologically or cytologically confirmed, advanced solid tumor that is refractory to standard therapy and/or for whom no further standard therapy is available
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2

Phase II

  • Adult patients >= 18 years old
  • Have a pathologically (histology or cytology) confirmed diagnosis of SCLC
  • Disease progression on or after at least one platinum-based standard chemotherapy regimen and/or an immune-checkpoint inhibitor for either limited or extensive stage disease.
  • Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • ECOG performance status of 0, 1 or 2

Phase II Expansion Cohorts

  • Have a pathologically (histology or cytology) confirmed diagnosis of urothelial carcinoma or metastatic, progressive, castrate resistant prostate cancer (mCRPC)
  • Disease progression on or after at least one platinum-based standard chemotherapy regimen and/or an immune-checkpoint inhibitor (except prostate cohort)
  • Have measurable disease per RECIST 1.1 (except prostate cohort)
  • Prior treatment with enzalutamide and/or abiraterone (prostate cancer cohort only)
  • Patients must have castrate levels of testosterone (<50 ng/dl [1.74 nmol/l]) (Prostate cohort only)

Design:

  • Patients meeting eligibility criteria will receive EP0057 (intravenous (IV) every (Q) 2weeks) plus olaparib (by mouth (PO) twice a day (BID), days 3-13 and days 17-26 administered in 28-day cycles, until disease progression or development of intolerable side effects. The maximum tolerated dose (MTD) of the combination will be used in Phase II.
  • Patients in Phase II will receive, the recommended phase 2 dose (RP2D) at DL4R EP0057 12 mg/m^2 and olaparib 250 mg twice a day (BID).
  • Blood, tumor and hair samples will be collected at multiple time points for pharmacokinetics (PK), pharmacodynamics (PD) analyses. Hair sample collection is optional. Tumor biopsies are optional for SCLC and ulcerative colitis (UC) patients and mandatory for metastatic castration-resistant prostate cancer (mCRPC) patients (only baseline biopsy is mandatory).
  • Toxicity will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
  • Tumor assessments will be made using computed tomography (CT) scans (chest, abdomen and pelvis) at baseline and after every 2 cycles (3 cycles for metastatic castration-resistant prostate cancer (mCRPC) according to RECIST version 1.1.
  • After discontinuation of study treatment, follow-up for survival will be carried out every 3 months.
Being tested
EP0057, olaparib, CT scan, CT chest, abdomen, and pelvis, Bone scan
Keywords
PARP Inhibitor, Topoisomerase I (Top1), Camptothecins, Nanoparticle Drug Conjugate, Solid Tumors
Medical subject headings
Carcinoma, Transitional Cell, Lung Neoplasms, Small Cell Lung Carcinoma, Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EP0057Drug

    Also called CRLX101

    EP0057 (formerly CRLX101) intravenous (IV) every (Q) 2weeks Day 1 and Day 15, administered in 28-day cycles, until disease progression or development of intolerable side effects.

    Plus olaparib (by mouth (PO) days 3-13* and days 17-26*) administered in 28-day cycles, until disease progression or development of intolerable side effects. Phase (P)1: Dose Escalation P2: recommended phase 2 dose (RP2D).

    (* On days 13 and 26, only one dose of olaparib will be administered in the morning)

  • olaparibDrug

    Also called Lynparza

    Olaparib (by mouth (PO) days 3-13* and days 17-26* administered in 28-day cycles, until disease progression or development of intolerable side effects Plus EP0057 (formerly CRLX101) (intravenous (IV) every (Q) 2 weeks, Day 1 and Day 15) administered in 28-day cycles, until disease progression or development of intolerable side effects. Phase (P)1: Dose Escalation P2: recommended phase 2 dose (RP2D).

    (* On days 13 and 26, only one dose of olaparib will be administered in the morning).

  • CT scanDiagnostic test

    Also called Computed tomography scan

    Screening and baseline.

  • CT chest, abdomen, and pelvisDiagnostic test

    Metastatic castration-resistant prostate cancer (mCRPC) participants only at screening, baseline, cycle 2 Day 1, and end of treatment/disease progression.

  • Bone scanDiagnostic test

    Also called Bone scintigraphy

    Metastatic castration-resistant prostate cancer (mCRPC) participants only at screening, baseline, cycle 2 Day 1, and end of treatment/disease progression.

  • ECGDiagnostic test

    Also called Electrocardiogram

    Screening, baseline, Day 1, Day 15 and cycle 2, Day 1.

  • EchocardiogramDiagnostic test

    Also called Echo

    At screening.

  • BiopsyProcedure or surgery

    Baseline Day 4 and end of treatment/disease progression.

Study groups in NCT02769962
Study groupRoleWhat they receive
1/Phase I - EP0057 (formerly CRLX101) + OlaparibExperimentalEP0057 + olaparib
Receives: Drug: EP0057; Drug: olaparib; Diagnostic Test: CT scan; Diagnostic Test: CT chest, abdomen, and pelvis; Diagnostic Test: Bone scan; Diagnostic Test: ECG; Diagnostic Test: Echocardiogram; Procedure: Biopsy
2/Phase II - EP0057 + Olaparib at Maximum Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)ExperimentalEP0057 (formerly CRLX101) + olaparib at maximum tolerated dose/recommended phase 2 dose (MTD/RP2D)
Receives: Drug: EP0057; Drug: olaparib; Diagnostic Test: CT scan; Diagnostic Test: CT chest, abdomen, and pelvis; Diagnostic Test: Bone scan; Diagnostic Test: ECG; Diagnostic Test: Echocardiogram; Procedure: Biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of EP0057 (CLRX101) in Participants With Refractory Cancers.

    MTD/RP2D is the dose level at which no more than 1 of up to 6 participants experience dose-limiting toxicity (DLT) during the DLT evaluation period, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. DLTs will be defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (Version 4). The following toxicities, occurring during cycle 1 of the study combination, will be considered DLTs if deemed drug-related: Grade 4 neutropenia complicated by fever ≥38.5C and/or documented infection; Grade 4 neutropenia that does not resolve within 7 days; Grade 4 thrombocytopenia that does not resolve within 7 days or grade 3-4 thrombocytopenia complicated with hemorrhage. Grade 4 anemia that does not resolve within 7 days despite optimal therapy; and inability to begin subsequent treatment course within 28 days of the scheduled date, due to study drug toxicity.

    Measured: First 28 days

  2. Phase I: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Olaparib in Participants With Refractory Cancers.

    MTD/RP2D is the dose level at which no more than 1 of up to 6 participants experience dose-limiting toxicity (DLT) during the DLT evaluation period, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. DLTs will be defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (Version 4). The following toxicities, occurring during cycle 1 of the study combination, will be considered DLTs if deemed drug-related: Grade 4 neutropenia complicated by fever ≥38.5C and/or documented infection; Grade 4 neutropenia that does not resolve within 7 days; Grade 4 thrombocytopenia that does not resolve within 7 days or grade 3-4 thrombocytopenia complicated with hemorrhage. Grade 4 anemia that does not resolve within 7 days despite optimal therapy; and inability to begin subsequent treatment course within 28 days of the scheduled date, due to study drug toxicity.

    Measured: First 28 days

  3. Number of Dose Limiting Toxicities (DLTs) During the First Cycle

    DLTs will be defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (Version 4). The following toxicities, occurring during cycle 1 of the study combination, will be considered DLTs if deemed drug-related: Grade 4 neutropenia complicated by fever ≥38.5C and/or documented infection; Grade 4 neutropenia that does not resolve within 7 days; Grade 4 thrombocytopenia that does not resolve within 7 days or grade 3-4 thrombocytopenia complicated with hemorrhage. Grade 4 anemia that does not resolve within 7 days despite optimal therapy; and inability to begin subsequent treatment course within 28 days of the scheduled date, due to study drug toxicity, and any Grade 3-4 non-hematologic toxicity except fatigue/asthenia <2 weeks in duration).

    Measured: First 28 days

  4. Expansion: Progression Free Survival (PFS) Rate in the Combination of Olaparib Plus EP0057 (CLRX101) at 16 Weeks in Small Cell Lung Cancer (SCLC) Participants

    Determine if slightly more than 50% of participants may be identified as being without progression by 16 weeks. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: 16 weeks

  5. Expansion: Overall Response Rate (Complete Response (CR) + Partial Response (PR) of EP0057 (CLRX101) Plus Olaparib in Participants With Urothelial Carcinoma

    Overall response rate is the best response recorded from the start of the treatment until disease progression/recurrence. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: 8 weeks

  6. Expansion: Overall Response Rate (Complete Response (CR) + Partial Response (PR) of EP0057 (CLRX101) Plus Olaparib in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

    Determine if slightly more than 50% of participants may be identified as being without progression by 12 weeks. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: 12 weeks

Secondary outcomes (11)

  1. Occurrences of Toxicities Including Toxicity Type and Severity (Grades 1, 2, and 3) With Probable Association to Study Regimen in Participants on Expansion Cohorts

    Occurrence is captured by subjective and objective data via participant assessment ad self-report. Toxicities including toxicity type and severity (Grades 1, 2, 3, and/or 4) with probable association to study regimen in participants on Expansion cohorts was measured by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening.

    Measured: Start of treatment through 30 days post last dose, an average of 8.26 months.

  2. Progression-free Survival (PFS) on Expansion Cohorts

    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

    Measured: Every 3 months post-treatment, up until date of death from any cause or an average of 9.57 months.

  3. Progression-free Survival (PFS) of the Combination

    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

    Measured: Duration of time from start of treatment to time of progression or death, whichever occurs first, up to 2.5 years

  4. Overall Survival (OS) of the Combination

    OS is defined as the date of on-study to the date of death from any cause or last follow up.

    Measured: Date of on-study to the date of death from any cause or last follow up, up to 2.5 years

  5. Prostate-specific Antigen (PSA) on Metastatic Castration-Resistant Prostate Cancer (mCRPC) Expansion Cohort Reported at Time of Documented Partial Response (PR) With an 80% Confidence Interval

    PSA levels in blood, date of cycle 1, Day 1 (C1D1) - Best response date. PSA levels were measured by the Enzyme-Linked Immunosorbent Assay (ELISA). Normal PSA level is ≤6.5 ng/mL for age 70-79 and an elevated level is not interpreted good or bad; a very high number is a strong indicator of prostate cancer; since this is a cohort of prostate cancer an elevated number is expected. Partial Response was assessed by the Response Evaluation Criteria in Solid Tumors in Solid Tumors (RECIST) guideline (version 1.1) and Prostate Cancer Clinical Trials Working Group criteria (PCWG2). Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: 40.71 weeks from start of treatment to best response date

  6. Prostate-specific Antigen (PSA) on Metastatic Castration-Resistant Prostate Cancer (mCRPC) Expansion Cohort Reported at Time of Documented Partial Response (PR) an 95% Confidence Interval

    PSA levels in blood were measured by the Enzyme-Linked Immunosorbent Assay (ELISA). Normal PSA level is ≤6.5 ng/mL for age 70-79 and an elevated level is not interpreted good or bad; a very high number is a strong indicator of prostate cancer; since this is a cohort of prostate cancer an elevated number is expected; it is noted that this number is decreased from the start of therapy. Partial Response was assessed by the Response Evaluation Criteria in Solid Tumors in Solid Tumors (RECIST) guideline (version 1.1) and Prostate Cancer Clinical Trials Working Group criteria (PCWG2). Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: 40.71 weeks from start of treatment to best response date.

  7. Duration of Response (DOR) of the Combination

    DOR is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. OS is determined from the start of treatment until death. Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

    Measured: At baseline and after every 2 cycles up until the date of first documented progression or an average of average 11.09 months.

  8. Occurrences of Toxicities Including Toxicity Type and Severity (Grades 1, 2, 3, 4 and/or 5) With Probable Association to Study Regimen in Participants on Solid Tumor Cohorts

    Occurrence is captured by subjective and objective data via participant assessment and self-report. Toxicities including toxicity type and severity (Grades 1, 2, 3, and/or 4) with probable association to study regimen in participants on Expansion cohorts was measured by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event (AE).

    Measured: Start of treatment through 30 days post last dose, up to 3.99 months

  9. Maximum Observed Plasma Concentration of EP0057 (Both the Total Drug and Released Camptothecin) and Olaparib

    Blood samples for pharmacokinetic (PK) analysis were collected at pre-dose, mid-infusion (30 minutes), end of infusion (EOI), and 1, 2, 12, 24, and 48 hours (hr) post-EOI. Samples were drawn into sodium heparin tubes, processed to plasma, and stored at -80°C. On Cycle 6 Day 1 (C6D1), additional samples were collected to evaluate EP0057 (CLRX101) accumulation and potential drug interactions. Total plasma concentrations of released camptothecin (CPT) were measured after acidification with 0.1 normality (N) hydrochloric acid (HCl) to stabilize the lactone form, followed by dilution and Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry, (UPLC-MS/MS) analysis. Noncompartmental analysis was used to calculate PK parameters. Concentrations below lower limit of quantification (LLOQ) was excluded. Maximum serum concentration (CMAX) values were recorded as observed.

    Measured: Cycle 1 (pre-dose, mid-infusion (30 minutes), end of infusion (EOI), and 1, 2, 12, 24, and 48 hours (hr) post-EOI); and Cycle 6 Day 1.

  10. Mean Change From Baseline γ- H2A Histone Family Member X (H2AX) Intensity in Plucked Hair Follicles

    Mean of each participant's value of baseline γH2AX intensity in plucked hair follicles after receiving the drug. The mean change of each participant would be calculated from available hair follicles (or eyebrows if scalp hairs are unobtainable) that contain a full intact follicle and sheath were collected (i.e., plucked) from participants scalp with forceps. Hair follicles were fluorescently stained for γ- H2A histone family member X (H2AX) analysis.

    Measured: 4 days

  11. Pharmacodynamic (PD) Activity of EP0057 in Tumor Biopsy Specimens

    Drug concentrations in tumor specimens.

    Measured: Baseline, Cycle 1, then every 2 cycles, and at progression

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2016 (estimated)
  2. Study start9 May 2016
  3. Primary completion19 Apr 2023
  4. Study completion4 Mar 2025

Why it stopped: Accrual and drug manufacturing and supply were discontinued in 2025.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02769962
Sponsor's protocol ID
160107
Other IDs
16-C-0107
Status last verified
Jul 2026
First submitted
11 May 2016
Last updated
13 Aug 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).

Publications

  • Fialkoff G, Takahashi N, Sharkia I, Gutin J, Hermoni N, Nirula M, Kumar R, Pongor L, Nichols S, Sciuto L, Parmar K, Desai P, Suresh P, Abel M, El Meskini R, Maoz M, Rottenberg Y, Nevo S, Nechushtan H, Peretz T, Roame D, Hubert A, Cohen JE, Salah A, Temper M, Grinshpun A, Weaver-Ohler Z, Rajan A, Figg WD Sr, Zick A, Sadeh R, Friedman N, Thomas A. Plasma nucleosome profiling reports on tumor burden and molecular subtypes in small cell lung cancer. J Clin Invest. 2026 Oct 1;136(19):e202151. doi: 10.1172/JCI202151. eCollection 2026 Oct 1.

    PubMed 42820295

  • Schmidt KT, Huitema ADR, Dorlo TPC, Peer CJ, Cordes LM, Sciuto L, Wroblewski S, Pommier Y, Madan RA, Thomas A, Figg WD. Population pharmacokinetic analysis of nanoparticle-bound and free camptothecin after administration of NLG207 in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2020 Oct;86(4):475-486. doi: 10.1007/s00280-020-04134-9. Epub 2020 Sep 8.

    PubMed 32897402

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing EP0057, olaparib and CT scan in people with Urothelial Carcinoma and Urothelial Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 110 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of EP0057 (CLRX101) in Participants With Refractory Cancers. (time frame: First 28 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02769962, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.

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